Our central hypotheses are that estrogen deficiency accounts for both the rapid transient phase of bone loss soon after menopause and the subsequent slow continuous phase associated with secondary hyperparathyroidism in aging women and contributes substantially to bone loss in aging men; and that estrogen deficiency acts by different mechanisms on various target tissues to produce the bone loss. These hypotheses arose from findings made in the Project during the current funding period and will be extended during the new funding period by testing subsidiary hypotheses to complete our understanding of how sex steroid deficiency leads to osteoporosis. They will be tested through the specific aim (1) To define certain unrecognized or controversial effects of estrogen (E)-deficiency on bone and calcium (Ca) homeostasis.